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Taal, H. Rob ; St Pourcain, Beate ; Thiering, Elisabeth ; Das, Shikta ; Mook-Kanamori, Dennis O. ; Warrington, Nicole M. ; Kaakinen, Marika ; Kreiner-Moller, Eskil ; Bradfield, Jonathan P. ; Freathy, Rachel M. ; Geller, Frank ; Guxens, Monica ; Cousminer, Diana L. ; Kerkhof, Marjan ; Timpson, Nicholas J. ; Ikram, M. Arfan ; Beilin, Lawrence J. ; Bonnelykke, Klaus ; Buxton, Jessica L. ; Charoen, Pimphen ; Chawes, Bo Lund Krogsgaard ; Eriksson, Johan ; Evans, David M. ; Hofman, Albert ; Kemp, John P. ; Kim, Cecilia E. ; Klopp, Norman ; Lahti, Jari ; Lye, Stephen J. ; McMahon, George ; Mentch, Frank D. ; Mueller-Nurasyid, Martina ; O'Reilly, Paul F. ; Prokopenko, Inga ; Rivadeneira, Fernando ; Steegers, Eric A. P. ; Sunyer, Jordi ; Tiesler, Carla ; Yaghootkar, Hanieh ; Breteler, Monique M. B. ; Debette, Stephanie ; Fornage, Myriam ; Gudnason, Vilmundur ; Launer, Lenore J. ; van der Lugt, Aad ; Mosley, Thomas H. ; Seshadri, Sudha ; Smith, Albert V. ; Vernooij, Meike W. ; Blakemore, Alexandra I. F. ; Chiavacci, Rosetta M. ; Feenstra, Bjarke ; Fernandez-Banet, Julio ; Grant, Struan F. A. ; Hartikainen, Anna-Liisa ; van der Heijden, Albert J. ; Iniguez, Carmen ; Lathrop, Mark ; McArdle, Wendy L. ; Molgaard, Anne ; Newnham, John P. ; Palmer, Lyle J. ; Palotie, Aarno ; Pouta, Annneli ; Ring, Susan M. ; Sovio, Ulla ; Standl, Marie ; Uitterlinden, Andre G. ; Wichmann, H-Erich ; Vissing, Nadja Hawwa ; DeCarli, Charles ; van Duijn, Cornelia M. ; McCarthy, Mark I. ; Koppelman, Gerard H. ; Estivill, Xavier ; Hattersley, Andrew T. ; Melbye, Mads ; Bisgaard, Hans ; Pennell, Craig E. ; Widen, Elisabeth ; Hakonarson, Hakon ; Smith, George Davey ; Heinrich, Joachim ; Jarvelin, Marjo-Riitta ; Jaddoe, Vincent W. V. ; Adair, Linda S. ; Ang, Wei ; Atalay, Mustafa ; van Beijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Bradfield, Jonathan P. ; Charoen, Pimphen ; Coin, Lachlan ; Cousminer, Diana L. ; Das, Shikta ; Davis, Oliver S. P. ; Elliott, Paul ; Evans, David M. ; Feenstra, Bjarke ; Flexeder, Claudia ; Frayling, Tim ; Freathy, Rachel M. ; Gaillard, Romy ; Geller, Frank ; Groen-Blokhuis, Maria ; Goh, Liang-Kee ; Guxens, Monica ; Haworth, Claire M. A. ; Hadley, Dexter ; Hebebrand, Johannes ; Hinney, Anke ; Hirschhorn, Joel N. ; Holloway, John W. ; Holst, Claus ; Hottenga, Jouke Jan ; Horikoshi, Momoko ; Huikari, Ville ; Hypponen, Elina ; Iniguez, Carmen ; Kaakinen, Marika ; Kilpelainen, Tuomas O. ; Kirin, Mirna ; Kowgier, Matthew ; Lakka, Hanna-Maaria ; Lange, Leslie A. ; Lawlor, Debbie A. ; Lehtimaki, Terho ; Lewin, Alex ; Lindgren, Cecilia ; Lindi, Virpi ; Maggi, Reedik ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Mook-Kanamori, Dennis O. ; Murray, Jeffrey C. ; Nivard, Michel ; Nohr, Ellen Aagaard ; Ntalla, Ioanna ; Oken, Emily ; O'Reilly, Paul F. ; Palmer, Lyle J. ; Panoutsopoulou, Kalliope ; Pararajasingham, Jennifer ; Prokopenko, Inga ; Rodriguez, Alina ; Salem, Rany M. ; Sebert, Sylvain ; Siitonen, Niina ; Sovio, Ulla ; St Pourcain, Beate ; Strachan, David P. ; Sunyer, Jordi ; Taal, H. Rob ; Teo, Yik-Ying ; Thiering, Elisabeth ; Tiesler, Carla ; Uitterlinden, Andre G. ; Valcarcel, Beatriz ; Warrington, Nicole M. ; White, Scott ; Willemsen, Gonneke ; Yaghootkar, Hanieh ; Zeggini, Eleftheria ; Boomsma, Dorret I. ; Cooper, Cyrus ; Estivill, Xavier ; Gillman, Matthew ; Grant, Struan F. A. ; Hakonarson, Hakon ; Hattersley, Andrew T. ; Heinrich, Joachim ; Hocher, Berthold ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; Lakka, Timo A. ; McCarthy, Mark I. ; Melbye, Mads ; Mohlke, Karen L. ; Dedoussis, George V. ; Ong, Ken K. ; Pearson, Ewan R. ; Pennell, Craig E. ; Price, Thomas S. ; Power, Chris ; Raitakari, Olli T. ; Saw, Seang-Mei ; Scherag, Andre ; Simell, Olli ; Sorensen, Thorkild I. A. ; Timpson, Nicholas J. ; Widen, Elisabeth ; Wilson, James F. ; Ang, Wei ; van Beijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Bradfield, Jonathan P. ; Charoen, Pimphen ; Coin, Lachlan ; Cousminer, Diana L. ; Das, Shikta ; Elliott, Paul ; Evans, David M. ; Frayling, Tim ; Freathy, Rachel M. ; Gaillard, Romy ; Groen-Blokhuis, Maria ; Guxens, Monica ; Hadley, Dexter ; Hottenga, Jouke Jan ; Huikari, Ville ; Hypponen, Elina ; Kaakinen, Marika ; Kowgier, Matthew ; Lawlor, Debbie A. ; Lewin, Alex ; Lindgren, Cecilia ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Mook-Kanamori, Dennis O. ; Nivard, Michel ; O'Reilly, Paul F. ; Palmer, Lyle J. ; Prokopenko, Inga ; Rodriguez, Alina ; Sebert, Sylvain ; Sovio, Ulla ; St Pourcain, Beate ; Standl, Marie ; Strachan, David P. ; Sunyer, Jordi ; Taal, H. Rob ; Thiering, Elisabeth ; Tiesler, Carla ; Uitterlinden, Andre G. ; Valcarcel, Beatriz ; Warrington, Nicole M. ; White, Scott ; Willemsen, Gonneke ; Yaghootkar, Hanieh ; Boomsma, Dorret I. ; Estivill, Xavier ; Grant, Struan F. A. ; Hakonarson, Hakon ; Hattersley, Andrew T. ; Heinrich, Joachim ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; McCarthy, Mark I. ; Pennell, Craig E. ; Power, Chris ; Timpson, Nicholas J. ; Widen, Elisabeth ; Ikram, M. Arfan ; Fornage, Myriam ; Smith, Albert V. ; Seshadri, Sudha ; Schmidt, Reinhold ; Debette, Stephanie ; Vrooman, Henri A. ; Sigurdsson, Sigurdur ; Ropele, Stefan ; Coker, Laura H. ; Longstreth, W. T. ; Niessen, Wiro J. ; DeStefano, Anita L. ; Beiser, Alexa ; Zijdenbos, Alex P. ; Struchalin, Maksim ; Jack, Clifford R. ; Nalls, Mike A. ; Au, Rhoda ; Hofman, Albert ; Gudnason, Haukur ; van der Lugt, Aad ; Harris, Tamara B. ; Meeks, William M. ; Vernooij, Meike W. ; van Buchem, Mark A. ; Catellier, Diane ; Gudnason, Vilmundur ; Windham, B. Gwen ; Wolf, Philip A. ; van Duijn, Cornelia M. ; Mosley, Thomas H. ; Schmidt, Helena ; Launer, Lenore J. ; Breteler, Monique M. B. ; DeCarli, Charles
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
Abdalla, Hassan E. ; Abramowski, Attila ; Aharonian, Felix A. ; Benkhali, Faiçal Ait ; Akhperjanian, A. G. ; Angüner, Ekrem Oǧuzhan ; Arrieta, M. ; Aubert, Pierre ; Backes, Michael ; Balzer, Arnim ; Barnard, Michelle ; Becherini, Yvonne ; Tjus, Julia Becker ; Berge, David ; Bernhard, Sabrina ; Bernlöhr, K. ; Birsin, E. ; Blackwell, R. ; Bottcher, Markus ; Boisson, Catherine ; Bolmont, J. ; Bordas, Pol ; Bregeon, Johan ; Brun, Francois ; Brun, Pierre ; Bryan, Mark ; Bulik, Tomasz ; Capasso, M. ; Carr, John ; Casanova, Sabrina ; Chakraborty, N. ; Chalme-Calvet, R. ; Chaves, Ryan C. G. ; Chen, Andrew ; Chevalier, J. ; Chretien, M. ; Colafrancesco, Sergio ; Cologna, Gabriele ; Condon, B. ; Conrad, Jan ; Couturier, C. ; Cui, Y. ; Davids, I. D. ; Degrange, B. ; Deil, Christoph ; deWilt, P. ; Djannati-Atai, Arache ; Domainko, Wilfried ; Donath, Axel ; Dubus, Guillaume ; Dutson, Kate ; Dyks, J. ; Dyrda, M. ; Edwards, T. ; Egberts, Kathrin ; Eger, P. ; Ernenwein, J. -P. ; Eschbach, S. ; Farnier, C. ; Fegan, Stuart ; Fernandes, M. V. ; Fiasson, A. ; Fontaine, G. ; Foerster, A. ; Funk, S. ; Füßling, Matthias ; Gabici, Stefano ; Gajdus, M. ; Gallant, Y. A. ; Garrigoux, T. ; Giavitto, Gianluca ; Giebels, B. ; Glicenstein, J. F. ; Gottschall, Daniel ; Goyal, A. ; Grondin, M. -H. ; Grudzinska, M. ; Hadasch, Daniela ; Hahn, J. ; Hawkes, J. ; Heinzelmann, G. ; Henri, Gilles ; Hermann, G. ; Hervet, Olivier ; Hillert, A. ; Hinton, James Anthony ; Hofmann, Werner ; Hoischen, Clemens ; Holler, M. ; Horns, D. ; Ivascenko, Alex ; Jacholkowska, A. ; Jamrozy, Marek ; Janiak, M. ; Jankowsky, D. ; Jankowsky, Felix ; Jingo, M. ; Jogler, Tobias ; Jouvin, Lea ; Jung-Richardt, Ira ; Kastendieck, M. A. ; Katarzynski, Krzysztof ; Katz, Uli ; Kerszberg, D. ; Khelifi, B. ; Kieffer, M. ; King, J. ; Klepser, S. ; Klochkov, Dmitry ; Kluzniak, W. ; Kolitzus, D. ; Komin, Nu. ; Kosack, K. ; Krakau, S. ; Kraus, Michael ; Krayzel, F. ; Kruger, P. P. ; Laffon, H. ; Lamanna, G. ; Lau, Jeanie ; Lees, J. -P. ; Lefaucheur, J. ; Lefranc, V. ; Lemiere, A. ; Lemoine-Goumard, M. ; Lenain, J. -P. ; Leser, Eva ; Lohse, Thomas ; Lorentz, M. ; Lui, R. ; Lypova, Iryna ; Marandon, Vincent ; Marcowith, Alexandre ; Mariaud, C. ; Marx, R. ; Maurin, G. ; Maxted, N. ; Mayer, Michael ; Meintjes, Petrus Johannes ; Menzler, U. ; Meyer, Manuel ; Mitchell, A. M. W. ; Moderski, R. ; Mohamed, M. ; Mora, K. ; Moulin, Emmanuel ; Murach, T. ; de Naurois, Mathieu ; Niederwanger, F. ; Niemiec, J. ; Oakes, L. ; Odaka, Hirokazu ; Ohm, Stefan ; Oettl, S. ; Ostrowski, M. ; Oya, I. ; Padovani, Marco ; Panter, M. ; Parsons, R. D. ; Arribas, M. Paz ; Pekeur, N. W. ; Pelletier, G. ; Petrucci, P. -O. ; Peyaud, B. ; Pita, S. ; Poon, Helen ; Prokhorov, Dmitry ; Prokoph, Heike ; Puehlhofer, Gerd ; Punch, Michael ; Quirrenbach, Andreas ; Raab, S. ; Reimer, Anita ; Reimer, Olaf ; Renaud, M. ; de los Reyes, R. ; Rieger, Frank ; Romoli, Carlo ; Rosier-Lees, S. ; Rowell, G. ; Rudak, B. ; Rulten, C. B. ; Sahakian, V. ; Salek, David ; Sanchez, David A. ; Santangelo, Andrea ; Sasaki, Manami ; Schlickeiser, Reinhard ; Schussler, F. ; Schulz, Andreas ; Schwanke, U. ; Schwemmer, S. ; Seyffert, A. S. ; Shafi, N. ; Simoni, R. ; Sol, H. ; Spanier, Felix ; Spengler, G. ; Spiess, F. ; Stawarz, Lukasz ; Steenkamp, R. ; Stegmann, Christian ; Stinzing, F. ; Stycz, K. ; Sushch, Iurii ; Tavernet, J. -P. ; Tavernier, T. ; Taylor, A. M. ; Terrier, R. ; Tluczykont, Martin ; Trichard, C. ; Tuffs, R. ; van der Walt, Johan ; van Eldik, Christopher ; van Soelen, Brian ; Vasileiadis, Georges ; Veh, J. ; Venter, C. ; Viana, A. ; Vincent, P. ; Vink, Jacco ; Voisin, F. ; Voelk, Heinrich J. ; Vuillaume, Thomas ; Wadiasingh, Z. ; Wagner, Stefan J. ; Wagner, P. ; Wagner, R. M. ; White, R. ; Wierzcholska, Alicja ; Willmann, P. ; Woernlein, A. ; Wouters, Denis ; Yang, R. ; Zabalza, Victor ; Zaborov, D. ; Zacharias, M. ; Zdziarski, A. A. ; Zech, Andreas ; Zefi, F. ; Ziegler, A. ; Zywucka, Natalia
The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section <sigma nu >. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach <sigma nu > values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe <sigma nu > values expected from the thermal relic density for TeV DM particles.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Wuttke, Matthias ; Li, Yong ; Li, Man ; Sieber, Karsten B. ; Feitosa, Mary F. ; Gorski, Mathias ; Tin, Adrienne ; Wang, Lihua ; Chu, Audrey Y. ; Hoppmann, Anselm ; Kirsten, Holger ; Giri, Ayush ; Chai, Jin-Fang ; Sveinbjornsson, Gardar ; Tayo, Bamidele O. ; Nutile, Teresa ; Fuchsberger, Christian ; Marten, Jonathan ; Cocca, Massimiliano ; Ghasemi, Sahar ; Xu, Yizhe ; Horn, Katrin ; Noce, Damia ; Van der Most, Peter J. ; Sedaghat, Sanaz ; Yu, Zhi ; Akiyama, Masato ; Afaq, Saima ; Ahluwalia, Tarunveer Singh ; Almgren, Peter ; Amin, Najaf ; Arnlov, Johan ; Bakker, Stephan J. L. ; Bansal, Nisha ; Baptista, Daniela ; Bergmann, Sven ; Biggs, Mary L. ; Biino, Ginevra ; Boehnke, Michael ; Boerwinkle, Eric ; Boissel, Mathilde ; Böttinger, Erwin ; Boutin, Thibaud S. ; Brenner, Hermann ; Brumat, Marco ; Burkhardt, Ralph ; Butterworth, Adam S. ; Campana, Eric ; Campbell, Archie ; Campbell, Harry ; Canouil, Mickael ; Carroll, Robert J. ; Catamo, Eulalia ; Chambers, John C. ; Chee, Miao-Ling ; Chee, Miao-Li ; Chen, Xu ; Cheng, Ching-Yu ; Cheng, Yurong ; Christensen, Kaare ; Cifkova, Renata ; Ciullo, Marina ; Concas, Maria Pina ; Cook, James P. ; Coresh, Josef ; Corre, Tanguy ; Sala, Cinzia Felicita ; Cusi, Daniele ; Danesh, John ; Daw, E. Warwick ; De Borst, Martin H. ; De Grandi, Alessandro ; De Mutsert, Renee ; De Vries, Aiko P. J. ; Degenhardt, Frauke ; Delgado, Graciela ; Demirkan, Ayse ; Di Angelantonio, Emanuele ; Dittrich, Katalin ; Divers, Jasmin ; Dorajoo, Rajkumar ; Eckardt, Kai-Uwe ; Ehret, Georg ; Elliott, Paul ; Endlich, Karlhans ; Evans, Michele K. ; Felix, Janine F. ; Foo, Valencia Hui Xian ; Franco, Oscar H. ; Franke, Andre ; Freedman, Barry I. ; Freitag-Wolf, Sandra ; Friedlander, Yechiel ; Froguel, Philippe ; Gansevoort, Ron T. ; Gao, He ; Gasparini, Paolo ; Gaziano, J. Michael ; Giedraitis, Vilmantas ; Gieger, Christian ; Girotto, Giorgia ; Giulianini, Franco ; Gogele, Martin ; Gordon, Scott D. ; Gudbjartsson, Daniel F. ; Gudnason, Vilmundur ; Haller, Toomas ; Hamet, Pavel ; Harris, Tamara B. ; Hartman, Catharina A. ; Hayward, Caroline ; Hellwege, Jacklyn N. ; Heng, Chew-Kiat ; Hicks, Andrew A. ; Hofer, Edith ; Huang, Wei ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Indridason, Olafur S. ; Ingelsson, Erik ; Ising, Marcus ; Jaddoe, Vincent W. V. ; Jakobsdottir, Johanna ; Jonas, Jost B. ; Joshi, Peter K. ; Josyula, Navya Shilpa ; Jung, Bettina ; Kahonen, Mika ; Kamatani, Yoichiro ; Kammerer, Candace M. ; Kanai, Masahiro ; Kastarinen, Mika ; Kerr, Shona M. ; Khor, Chiea-Chuen ; Kiess, Wieland ; Kleber, Marcus E. ; Koenig, Wolfgang ; Kooner, Jaspal S. ; Korner, Antje ; Kovacs, Peter ; Kraja, Aldi T. ; Krajcoviechova, Alena ; Kramer, Holly ; Kramer, Bernhard K. ; Kronenberg, Florian ; Kubo, Michiaki ; Kuhnel, Brigitte ; Kuokkanen, Mikko ; Kuusisto, Johanna ; La Bianca, Martina ; Laakso, Markku ; Lange, Leslie A. ; Langefeld, Carl D. ; Lee, Jeannette Jen-Mai ; Lehne, Benjamin ; Lehtimaki, Terho ; Lieb, Wolfgang ; Lim, Su-Chi ; Lind, Lars ; Lindgren, Cecilia M. ; Liu, Jun ; Liu, Jianjun ; Loeffler, Markus ; Loos, Ruth J. F. ; Lucae, Susanne ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Magi, Reedik ; Magnusson, Patrik K. E. ; Mahajan, Anubha ; Martin, Nicholas G. ; Martins, Jade ; Marz, Winfried ; Mascalzoni, Deborah ; Matsuda, Koichi ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Metspalu, Andres ; Mikaelsdottir, Evgenia K. ; Milaneschi, Yuri ; Miliku, Kozeta ; Mishra, Pashupati P. ; Program, V. A. Million Veteran ; Mohlke, Karen L. ; Mononen, Nina ; Montgomery, Grant W. ; Mook-Kanamori, Dennis O. ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nalls, Mike A. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; Noordam, Raymond ; Olafsson, Isleifur ; Oldehinkel, Albertine J. ; Orho-Melander, Marju ; Ouwehand, Willem H. ; Padmanabhan, Sandosh ; Palmer, Nicholette D. ; Palsson, Runolfur ; Penninx, Brenda W. J. H. ; Perls, Thomas ; Perola, Markus ; Pirastu, Mario ; Pirastu, Nicola ; Pistis, Giorgio ; Podgornaia, Anna I. ; Polasek, Ozren ; Ponte, Belen ; Porteous, David J. ; Poulain, Tanja ; Pramstaller, Peter P. ; Preuss, Michael H. ; Prins, Bram P. ; Province, Michael A. ; Rabelink, Ton J. ; Raffield, Laura M. ; Raitakari, Olli T. ; Reilly, Dermot F. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Ridker, Paul M. ; Rivadeneira, Fernando ; Rizzi, Federica ; Roberts, David J. ; Robino, Antonietta ; Rossing, Peter ; Rudan, Igor ; Rueedi, Rico ; Ruggiero, Daniela ; Ryan, Kathleen A. ; Saba, Yasaman ; Sabanayagam, Charumathi ; Salomaa, Veikko ; Salvi, Erika ; Saum, Kai-Uwe ; Schmidt, Helena ; Schmidt, Reinhold ; Ben Schottker ; Schulz, Christina-Alexandra ; Schupf, Nicole ; Shaffer, Christian M. ; Shi, Yuan ; Smith, Albert V. ; Smith, Blair H. ; Soranzo, Nicole ; Spracklen, Cassandra N. ; Strauch, Konstantin ; Stringham, Heather M. ; Stumvoll, Michael ; Svensson, Per O. ; Szymczak, Silke ; Tai, E-Shyong ; Tajuddin, Salman M. ; Tan, Nicholas Y. Q. ; Taylor, Kent D. ; Teren, Andrej ; Tham, Yih-Chung ; Thiery, Joachim ; Thio, Chris H. L. ; Thomsen, Hauke ; Thorleifsson, Gudmar ; Toniolo, Daniela ; Tonjes, Anke ; Tremblay, Johanne ; Tzoulaki, Ioanna ; Uitterlinden, Andre G. ; Vaccargiu, Simona ; Van Dam, Rob M. ; Van der Harst, Pim ; Van Duijn, Cornelia M. ; Edward, Digna R. Velez ; Verweij, Niek ; Vogelezang, Suzanne ; Volker, Uwe ; Vollenweider, Peter ; Waeber, Gerard ; Waldenberger, Melanie ; Wallentin, Lars ; Wang, Ya Xing ; Wang, Chaolong ; Waterworth, Dawn M. ; Bin Wei, Wen ; White, Harvey ; Whitfield, John B. ; Wild, Sarah H. ; Wilson, James F. ; Wojczynski, Mary K. ; Wong, Charlene ; Wong, Tien-Yin ; Xu, Liang ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Weihua ; Zonderman, Alan B. ; Rotter, Jerome I. ; Bochud, Murielle ; Psaty, Bruce M. ; Vitart, Veronique ; Wilson, James G. ; Dehghan, Abbas ; Parsa, Afshin ; Chasman, Daniel I. ; Ho, Kevin ; Morris, Andrew P. ; Devuyst, Olivier ; Akilesh, Shreeram ; Pendergrass, Sarah A. ; Sim, Xueling ; Boger, Carsten A. ; Okada, Yukinori ; Edwards, Todd L. ; Snieder, Harold ; Stefansson, Kari ; Hung, Adriana M. ; Heid, Iris M. ; Scholz, Markus ; Teumer, Alexander ; Kottgen, Anna ; Pattaro, Cristian
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Khider, D. ; Emile-Geay, J. ; McKay, N. P. ; Gil, Y. ; Garijo, D. ; Ratnakar, V ; Alonso-Garcia, M. ; Bertrand, S. ; Bothe, O. ; Brewer, P. ; Bunn, A. ; Chevalier, M. ; Comas-Bru, L. ; Csank, A. ; Dassie, E. ; DeLong, K. ; Felis, T. ; Francus, P. ; Frappier, A. ; Gray, W. ; Goring, S. ; Jonkers, L. ; Kahle, M. ; Kaufman, D. ; Kehrwald, N. M. ; Martrat, B. ; McGregor, H. ; Richey, J. ; Schmittner, A. ; Scroxton, N. ; Sutherland, E. ; Thirumalai, Kaustubh ; Allen, K. ; Arnaud, F. ; Axford, Y. ; Barrows, T. ; Bazin, L. ; Birch, S. E. Pilaar ; Bradley, E. ; Bregy, J. ; Capron, E. ; Cartapanis, O. ; Chiang, H-W ; Cobb, K. M. ; Debret, M. ; Dommain, Réne ; Du, J. ; Dyez, K. ; Emerick, S. ; Erb, M. P. ; Falster, G. ; Finsinger, W. ; Fortier, D. ; Gauthier, Nicolas ; George, S. ; Grimm, E. ; Hertzberg, J. ; Hibbert, F. ; Hillman, A. ; Hobbs, W. ; Huber, M. ; Hughes, A. L. C. ; Jaccard, S. ; Ruan, J. ; Kienast, M. ; Konecky, B. ; Le Roux, G. ; Lyubchich, V ; Novello, V. F. ; Olaka, L. ; Partin, J. W. ; Pearce, C. ; Phipps, S. J. ; Pignol, C. ; Piotrowska, N. ; Poli, M-S ; Prokopenko, A. ; Schwanck, F. ; Stepanek, C. ; Swann, G. E. A. ; Telford, R. ; Thomas, E. ; Thomas, Z. ; Truebe, S. ; von Gunten, L. ; Waite, A. ; Weitzel, N. ; Wilhelm, B. ; Williams, J. ; Winstrup, M. ; Zhao, N. ; Zhou, Y.
The progress of science is tied to the standardization of measurements, instruments, and data. This is especially true in the Big Data age, where analyzing large data volumes critically hinges on the data being standardized. Accordingly, the lack of community-sanctioned data standards in paleoclimatology has largely precluded the benefits of Big Data advances in the field. Building upon recent efforts to standardize the format and terminology of paleoclimate data, this article describes the Paleoclimate Community reporTing Standard (PaCTS), a crowdsourced reporting standard for such data. PaCTS captures which information should be included when reporting paleoclimate data, with the goal of maximizing the reuse value of paleoclimate data sets, particularly for synthesis work and comparison to climate model simulations. Initiated by the LinkedEarth project, the process to elicit a reporting standard involved an international workshop in 2016, various forms of digital community engagement over the next few years, and grassroots working groups. Participants in this process identified important properties across paleoclimate archives, in addition to the reporting of uncertainties and chronologies; they also identified archive-specific properties and distinguished reporting standards for new versus legacy data sets. This work shows that at least 135 respondents overwhelmingly support a drastic increase in the amount of metadata accompanying paleoclimate data sets. Since such goals are at odds with present practices, we discuss a transparent path toward implementing or revising these recommendations in the near future, using both bottom-up and top-down approaches.
Abramowski, Attila ; Aharonian, Felix A. ; Benkhali, Faical Ait ; Akhperjanian, A. G. ; Angüner, Ekrem Oǧuzhan ; Backes, Michael ; Balenderan, Shangkari ; Balzer, Arnim ; Barnacka, Anna ; Becherini, Yvonne ; Tjus, Julia Becker ; Berge, David ; Bernhard, Sabrina ; Bernlöhr, Konrad ; Birsin, E. ; Biteau, Jonathan ; Böttcher, Markus ; Boisson, Catherine ; Bolmont, J. ; Bordas, Pol ; Bregeon, Johan ; Brun, Francois ; Brun, Pierre ; Bryan, Mark ; Bulik, Tomasz ; Carrigan, Svenja ; Casanova, Sabrina ; Chadwick, Paula M. ; Chakraborty, Nachiketa ; Chalme-Calvet, R. ; Chaves, Ryan C. G. ; Chretien, M. ; Colafrancesco, Sergio ; Cologna, Gabriele ; Conrad, Jan ; Couturier, Claire ; Cui, Yudong ; Davids, Isak Delberth ; Degrange, Bernhard ; Deil, Christoph ; deWilt, P. ; Djannati-Ataï, A. ; Domainko, Wilfried ; Donath, Axel ; Dubus, G. ; Dutson, K. ; Dyks, J. ; Dyrda, M. ; Edwards, Tanya ; Egberts, Kathrin ; Eger, Peter ; Espigat, P. ; Farnier, C. ; Fegan, Stephen ; Feinstein, Fabrice ; Fernandes, Milton Virgilio ; Fernandez, Diane ; Fiasson, A. ; Fontaine, Gerard ; Förster, Andreas ; Fuessling, M. ; Gabici, S. ; Gajdus, M. ; Gallant, Yves A. ; Garrigoux, Tania ; Giavitto, G. ; Giebels, Berrie ; Glicenstein, Jean-Francois ; Gottschall, Daniel ; Grondin, M. -H. ; Grudzinska, M. ; Hadasch, Daniela ; Haeffner, S. ; Hahn, Joachim ; Harris, Jonathan ; Heinzelmann, Götz ; Henri, G. ; Hermann, German ; Hervet, O. ; Hillert, Andreas ; Hinton, James Anthony ; Hofmann, Werner ; Hofverberg, Petter ; Holler, Markus ; Horns, Dieter ; Ivascenko, Alex ; Jacholkowska, A. ; Jahn, C. ; Jamrozy, Marek ; Janiak, M. ; Jankowsky, F. ; Jung-Richardt, I. ; Kastendieck, Max Anton ; Katarzynski, K. ; Katz, U. ; Kaufmann, S. ; Khelifi, B. ; Kieffer, Michel ; Klepser, S. ; Klochkov, Dmitry ; Kluzniak, W. ; Kolitzus, David ; Komin, Nu ; Kosack, Karl ; Krakau, Steffen ; Krayzel, F. ; Krueger, Pat P. ; Laffon, H. ; Lamanna, G. ; Lefaucheur, J. ; Lefranc, Valentin ; Lemiere, A. ; Lemoine-Goumard, M. ; Lenain, J. -P. ; Lohse, Thomas ; Lopatin, A. ; Lu, Chia-Chun ; Marandon, Vincent ; Marcowith, Alexandre ; Marx, Ramin ; Maurin, G. ; Maxted, Nigel ; Mayer, Michael ; McComb, T. J. Lowry ; Mehault, J. ; Meintjes, P. J. ; Menzler, Ulf ; Meyer, M. ; Mitchell, Alison M. W. ; Moderski, R. ; Mohamed, M. ; Mora, K. ; Moulin, Emmanuel ; Murach, Thomas ; de Naurois, Mathieu ; Niemiec, J. ; Nolan, Sam J. ; Oakes, Louise ; Odaka, Hirokazu ; Ohm, S. ; Optiz, Björn ; Ostrowski, Michal ; Oya, I. ; Panter, Michael ; Parsons, R. Daniel ; Arribas, M. Paz ; Pekeur, Nikki W. ; Pelletier, G. ; Petrucci, P. -O. ; Peyaud, B. ; Pita, S. ; Poon, Helen ; Pühlhofer, Gerd ; Punch, M. ; Quirrenbach, A. ; Raab, S. ; Reichardt, I. ; Reimer, Anita ; Reimer, Olaf ; Renaud, Metz ; de los Reyes, Raquel ; Rieger, Frank ; Romoli, C. ; Rosier-Lees, S. ; Rowell, G. ; Rudak, B. ; Rulten, C. B. ; Sahakian, Vardan ; Salek, D. ; Sanchez, David M. ; Santangelo, Andrea ; Schlickeiser, Reinhard ; Schuessler, F. ; Schulz, A. ; Schwanke, Ullrich ; Schwarzburg, S. ; Schwemmer, S. ; Sol, H. ; Spanier, Felix ; Spengler, G. ; Spies, Franziska ; Stawarz, Lukasz ; Steenkamp, Riaan ; Stegmann, Christian ; Stinzing, F. ; Stycz, K. ; Sushch, Iurii ; Tavernet, J. -P. ; Tavernier, T. ; Taylor, A. M. ; Terrier, R. ; Tluczykont, Martin ; Trichard, C. ; Valerius, K. ; van Eldik, C. ; van Soelen, B. ; Vasileiadis, Georges ; Veh, J. ; Venter, Christo ; Viana, Aion ; Vincent, P. ; Vink, Jacco ; Völk, Heinrich J. ; Volpe, Francesca ; Vorster, Martine ; Vuillaume, T. ; Wagner, S. J. ; Wagner, P. ; Wagner, R. M. ; Ward, Martin ; Weidinger, Matthias ; Weitzel, Quirin ; White, R. ; Wierzcholska, A. ; Willmann, P. ; Woernlein, A. ; Wouters, D. ; Yang, Ruizhi ; Zabalza, Victor ; Zaborov, Dmitry ; Zacharias, M. ; Zdziarski, A. A. ; Zech, Alraune ; Zechlin, Hannes -S.
Read, Betsy A. ; Kegel, Jessica ; Klute, Mary J. ; Kuo, Alan ; Lefebvre, Stephane C. ; Maumus, Florian ; Mayer, Christoph ; Miller, John ; Monier, Adam ; Salamov, Asaf ; Young, Jeremy ; Aguilar, Maria ; Claverie, Jean-Michel ; Frickenhaus, Stephan ; Gonzalez, Karina ; Herman, Emily K. ; Lin, Yao-Cheng ; Napier, Johnathan ; Ogata, Hiroyuki ; Sarno, Analissa F. ; Shmutz, Jeremy ; Schroeder, Declan ; de Vargas, Colomban ; Verret, Frederic ; von Dassow, Peter ; Valentin, Klaus ; Van de Peer, Yves ; Wheeler, Glen ; Dacks, Joel B. ; Delwiche, Charles F. ; Dyhrman, Sonya T. ; Glöckner, Gernot ; John, Uwe ; Richards, Thomas ; Worden, Alexandra Z. ; Zhang, Xiaoyu ; Grigoriev, Igor V. ; Allen, Andrew E. ; Bidle, Kay ; Borodovsky, M. ; Bowler, C. ; Brownlee, Colin ; Cock, J. Mark ; Elias, Marek ; Gladyshev, Vadim N. ; Groth, Marco ; Guda, Chittibabu ; Hadaegh, Ahmad ; Iglesias-Rodriguez, Maria Debora ; Jenkins, J. ; Jones, Bethan M. ; Lawson, Tracy ; Leese, Florian ; Lindquist, Erika ; Lobanov, Alexei ; Lomsadze, Alexandre ; Malik, Shehre-Banoo ; Marsh, Mary E. ; Mackinder, Luke ; Mock, Thomas ; Müller-Röber, Bernd ; Pagarete, Antonio ; Parker, Micaela ; Probert, Ian ; Quesneville, Hadi ; Raines, Christine ; Rensing, Stefan A. ; Riano-Pachon, Diego Mauricio ; Richier, Sophie ; Rokitta, Sebastian ; Shiraiwa, Yoshihiro ; Soanes, Darren M. ; van der Giezen, Mark ; Wahlund, Thomas M. ; Williams, Bryony ; Wilson, Willie ; Wolfe, Gordon ; Wurch, Louie L.
Coccolithophores have influenced the global climate for over 200 million years(1). These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems(2). They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering them visible from space(3). Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean(4). Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions.
Right on track?
(2019)
Hofman, Maarten P. G. ; Hayward, M. W. ; Heim, M. ; Marchand, P. ; Rolandsen, C. M. ; Mattisson, Jenny ; Urbano, F. ; Heurich, M. ; Mysterud, A. ; Melzheimer, J. ; Morellet, N. ; Voigt, Ulrich ; Allen, B. L. ; Gehr, Benedikt ; Rouco Zufiaurre, Carlos ; Ullmann, Wiebke ; Holand, O. ; Jorgensen, n H. ; Steinheim, G. ; Cagnacci, F. ; Kroeschel, M. ; Kaczensky, P. ; Buuveibaatar, B. ; Payne, J. C. ; Palmegiani, I ; Jerina, K. ; Kjellander, P. ; Johansson, O. ; LaPoint, S. ; Bayrakcismith, R. ; Linnell, J. D. C. ; Zaccaroni, M. ; Jorge, M. L. S. ; Oshima, J. E. F. ; Songhurst, A. ; Fischer, C. ; Mc Bride, R. T. ; Thompson, J. J. ; Streif, S. ; Sandfort, R. ; Bonenfant, Christophe ; Drouilly, M. ; Klapproth, M. ; Zinner, Dietmar ; Yarnell, Richard ; Stronza, A. ; Wilmott, L. ; Meisingset, E. ; Thaker, Maria ; Vanak, A. T. ; Nicoloso, S. ; Graeber, R. ; Said, S. ; Boudreau, M. R. ; Devlin, A. ; Hoogesteijn, R. ; May-Junior, J. A. ; Nifong, J. C. ; Odden, J. ; Quigley, H. B. ; Tortato, F. ; Parker, D. M. ; Caso, A. ; Perrine, J. ; Tellaeche, C. ; Zieba, F. ; Zwijacz-Kozica, T. ; Appel, C. L. ; Axsom, I ; Bean, W. T. ; Cristescu, B. ; Periquet, S. ; Teichman, K. J. ; Karpanty, S. ; Licoppe, A. ; Menges, V ; Black, K. ; Scheppers, Thomas L. ; Schai-Braun, S. C. ; Azevedo, F. C. ; Lemos, F. G. ; Payne, A. ; Swanepoel, L. H. ; Weckworth, B. ; Berger, A. ; Bertassoni, Alessandra ; McCulloch, G. ; Sustr, P. ; Athreya, V ; Bockmuhl, D. ; Casaer, J. ; Ekori, A. ; Melovski, D. ; Richard-Hansen, C. ; van de Vyver, D. ; Reyna-Hurtado, R. ; Robardet, E. ; Selva, N. ; Sergiel, A. ; Farhadinia, M. S. ; Sunde, P. ; Portas, R. ; Ambarli, Hüseyin ; Berzins, R. ; Kappeler, P. M. ; Mann, G. K. ; Pyritz, L. ; Bissett, C. ; Grant, T. ; Steinmetz, R. ; Swedell, Larissa ; Welch, R. J. ; Armenteras, D. ; Bidder, O. R. ; Gonzalez, T. M. ; Rosenblatt, A. ; Kachel, S. ; Balkenhol, N.
Satellite telemetry is an increasingly utilized technology in wildlife research, and current devices can track individual animal movements at unprecedented spatial and temporal resolutions. However, as we enter the golden age of satellite telemetry, we need an in-depth understanding of the main technological, species-specific and environmental factors that determine the success and failure of satellite tracking devices across species and habitats. Here, we assess the relative influence of such factors on the ability of satellite telemetry units to provide the expected amount and quality of data by analyzing data from over 3,000 devices deployed on 62 terrestrial species in 167 projects worldwide. We evaluate the success rate in obtaining GPS fixes as well as in transferring these fixes to the user and we evaluate failure rates. Average fix success and data transfer rates were high and were generally better predicted by species and unit characteristics, while environmental characteristics influenced the variability of performance. However, 48% of the unit deployments ended prematurely, half of them due to technical failure. Nonetheless, this study shows that the performance of satellite telemetry applications has shown improvements over time, and based on our findings, we provide further recommendations for both users and manufacturers.
Ikram, M. Arfan ; Fornage, Myriam ; Smith, Albert V. ; Seshadri, Sudha ; Schmidt, Reinhold ; Debette, Stephanie ; Vrooman, Henri A. ; Sigurdsson, Sigurdur ; Ropele, Stefan ; Taal, H. Rob ; Mook-Kanamori, Dennis O. ; Coker, Laura H. ; Longstreth, W. T. ; Niessen, Wiro J. ; DeStefano, Anita L. ; Beiser, Alexa ; Zijdenbos, Alex P. ; Struchalin, Maksim ; Jack, Clifford R. ; Rivadeneira, Fernando ; Uitterlinden, Andre G. ; Knopman, David S. ; Hartikainen, Anna-Liisa ; Pennell, Craig E. ; Thiering, Elisabeth ; Steegers, Eric A. P. ; Hakonarson, Hakon ; Heinrich, Joachim ; Palmer, Lyle J. ; Jarvelin, Marjo-Riitta ; McCarthy, Mark I. ; Grant, Struan F. A. ; St Pourcain, Beate ; Timpson, Nicholas J. ; Smith, George Davey ; Sovio, Ulla ; Nalls, Mike A. ; Au, Rhoda ; Hofman, Albert ; Gudnason, Haukur ; van der Lugt, Aad ; Harris, Tamara B. ; Meeks, William M. ; Vernooij, Meike W. ; van Buchem, Mark A. ; Catellier, Diane ; Jaddoe, Vincent W. V. ; Gudnason, Vilmundur ; Windham, B. Gwen ; Wolf, Philip A. ; van Duijn, Cornelia M. ; Mosley, Thomas H. ; Schmidt, Helena ; Launer, Lenore J. ; Breteler, Monique M. B. ; DeCarli, Charles ; Adair, Linda S. ; Ang, Wei ; Atalay, Mustafa ; vanBeijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Coin, Lachlan ; Davis, Oliver S. P. ; Elliott, Paul ; Flexeder, Claudia ; Frayling, Tim ; Gaillard, Romy ; Groen-Blokhuis, Maria ; Goh, Liang-Kee ; Haworth, Claire M. A. ; Hadley, Dexter ; Hebebrand, Johannes ; Hinney, Anke ; Hirschhorn, Joel N. ; Holloway, John W. ; Holst, Claus ; Hottenga, Jouke Jan ; Horikoshi, Momoko ; Huikari, Ville ; Hypponen, Elina ; Kilpelainen, Tuomas O. ; Kirin, Mirna ; Kowgier, Matthew ; Lakka, Hanna-Maaria ; Lange, Leslie A. ; Lawlor, Debbie A. ; Lehtimaki, Terho ; Lewin, Alex ; Lindgren, Cecilia ; Lindi, Virpi ; Maggi, Reedik ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Murray, Jeffrey C. ; Nivard, Michel ; Nohr, Ellen Aagaard ; Ntalla, Ioanna ; Oken, Emily ; Panoutsopoulou, Kalliope ; Pararajasingham, Jennifer ; Rodriguez, Alina ; Salem, Rany M. ; Sebert, Sylvain ; Siitonen, Niina ; Strachan, David P. ; Teo, Yik-Ying ; Valcarcel, Beatriz ; Willemsen, Gonneke ; Zeggini, Eleftheria ; Boomsma, Dorret I. ; Cooper, Cyrus ; Gillman, Matthew ; Hocher, Berthold ; Lakka, Timo A. ; Mohlke, Karen L. ; Dedoussis, George V. ; Ong, Ken K. ; Pearson, Ewan R. ; Price, Thomas S. ; Power, Chris ; Raitakari, Olli T. ; Saw, Seang-Mei ; Scherag, Andre ; Simell, Olli ; Sorensen, Thorkild I. A. ; Wilson, James F.
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
Gorski, Mathias ; Jung, Bettina ; Li, Yong ; Matias-Garcia, Pamela R. ; Wuttke, Matthias ; Coassin, Stefan ; Thio, Chris H. L. ; Kleber, Marcus E. ; Winkler, Thomas W. ; Wanner, Veronika ; Chai, Jin-Fang ; Chu, Audrey Y. ; Cocca, Massimiliano ; Feitosa, Mary F. ; Ghasemi, Sahar ; Hoppmann, Anselm ; Horn, Katrin ; Li, Man ; Nutile, Teresa ; Scholz, Markus ; Sieber, Karsten B. ; Teumer, Alexander ; Tin, Adrienne ; Wang, Judy ; Tayo, Bamidele O. ; Ahluwalia, Tarunveer S. ; Almgren, Peter ; Bakker, Stephan J. L. ; Banas, Bernhard ; Bansal, Nisha ; Biggs, Mary L. ; Boerwinkle, Eric ; Böttinger, Erwin ; Brenner, Hermann ; Carroll, Robert J. ; Chalmers, John ; Chee, Miao-Li ; Chee, Miao-Ling ; Cheng, Ching-Yu ; Coresh, Josef ; de Borst, Martin H. ; Degenhardt, Frauke ; Eckardt, Kai-Uwe ; Endlich, Karlhans ; Franke, Andre ; Freitag-Wolf, Sandra ; Gampawar, Piyush ; Gansevoort, Ron T. ; Ghanbari, Mohsen ; Gieger, Christian ; Hamet, Pavel ; Ho, Kevin ; Hofer, Edith ; Holleczek, Bernd ; Foo, Valencia Hui Xian ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Josyula, Navya Shilpa ; Kahonen, Mika ; Khor, Chiea-Chuen ; Koenig, Wolfgang ; Kramer, Holly ; Kraemer, Bernhard K. ; Kuehnel, Brigitte ; Lange, Leslie A. ; Lehtimaki, Terho ; Lieb, Wolfgang ; Loos, Ruth J. F. ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Milaneschi, Yuri ; Mishra, Pashupati P. ; Mononen, Nina ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; O'Donoghue, Michelle L. ; Orho-Melander, Marju ; Pendergrass, Sarah A. ; Penninx, Brenda W. J. H. ; Preuss, Michael H. ; Psaty, Bruce M. ; Raffield, Laura M. ; Raitakari, Olli T. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Rosenkranz, Alexander R. ; Rossing, Peter ; Rotter, Jerome ; Sabanayagam, Charumathi ; Schmidt, Helena ; Schmidt, Reinhold ; Schoettker, Ben ; Schulz, Christina-Alexandra ; Sedaghat, Sanaz ; Shaffer, Christian M. ; Strauch, Konstantin ; Szymczak, Silke ; Taylor, Kent D. ; Tremblay, Johanne ; Chaker, Layal ; van der Harst, Pim ; van der Most, Peter J. ; Verweij, Niek ; Voelker, Uwe ; Waldenberger, Melanie ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey D. ; Wilson, James G. ; Wong, Tien-Yin ; Woodward, Mark ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Yan ; Snieder, Harold ; Wanner, Christoph ; Boger, Carsten A. ; Kottgen, Anna ; Kronenberg, Florian ; Pattaro, Cristian ; Heid, Iris M.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Gorski, Mathias ; Jung, Bettina ; Li, Yong ; Matias-Garcia, Pamela R. ; Wuttke, Matthias ; Coassin, Stefan ; Thio, Chris H. L. ; Kleber, Marcus E. ; Winkler, Thomas W. ; Wanner, Veronika ; Chai, Jin-Fang ; Chu, Audrey Y. ; Cocca, Massimiliano ; Feitosa, Mary F. ; Ghasemi, Sahar ; Hoppmann, Anselm ; Horn, Katrin ; Li, Man ; Nutile, Teresa ; Scholz, Markus ; Sieber, Karsten B. ; Teumer, Alexander ; Tin, Adrienne ; Wang, Judy ; Tayo, Bamidele O. ; Ahluwalia, Tarunveer S. ; Almgren, Peter ; Bakker, Stephan J. L. ; Banas, Bernhard ; Bansal, Nisha ; Biggs, Mary L. ; Boerwinkle, Eric ; Böttinger, Erwin ; Brenner, Hermann ; Carroll, Robert J. ; Chalmers, John ; Chee, Miao-Li ; Chee, Miao-Ling ; Cheng, Ching-Yu ; Coresh, Josef ; de Borst, Martin H. ; Degenhardt, Frauke ; Eckardt, Kai-Uwe ; Endlich, Karlhans ; Franke, Andre ; Freitag-Wolf, Sandra ; Gampawar, Piyush ; Gansevoort, Ron T. ; Ghanbari, Mohsen ; Gieger, Christian ; Hamet, Pavel ; Ho, Kevin ; Hofer, Edith ; Holleczek, Bernd ; Foo, Valencia Hui Xian ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Josyula, Navya Shilpa ; Kahonen, Mika ; Khor, Chiea-Chuen ; Koenig, Wolfgang ; Kramer, Holly ; Kraemer, Bernhard K. ; Kuehnel, Brigitte ; Lange, Leslie A. ; Lehtimaki, Terho ; Lieb, Wolfgang ; Loos, Ruth J. F. ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Milaneschi, Yuri ; Mishra, Pashupati P. ; Mononen, Nina ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; O'Donoghue, Michelle L. ; Orho-Melander, Marju ; Pendergrass, Sarah A. ; Penninx, Brenda W. J. H. ; Preuss, Michael H. ; Psaty, Bruce M. ; Raffield, Laura M. ; Raitakari, Olli T. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Rosenkranz, Alexander R. ; Rossing, Peter ; Rotter, Jerome ; Sabanayagam, Charumathi ; Schmidt, Helena ; Schmidt, Reinhold ; Schoettker, Ben ; Schulz, Christina-Alexandra ; Sedaghat, Sanaz ; Shaffer, Christian M. ; Strauch, Konstantin ; Szymczak, Silke ; Taylor, Kent D. ; Tremblay, Johanne ; Chaker, Layal ; van der Harst, Pim ; van der Most, Peter J. ; Verweij, Niek ; Voelker, Uwe ; Waldenberger, Melanie ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey D. ; Wilson, James G. ; Wong, Tien-Yin ; Woodward, Mark ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Yan ; Snieder, Harold ; Wanner, Christoph ; Boger, Carsten A. ; Kottgen, Anna ; Kronenberg, Florian ; Pattaro, Cristian ; Heid, Iris M.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.